This invention relates to compounds that are 4-oxo-2 butenoic acid and 3-hydrazino-2,4-dioxobutanoic acid derivatives and more particularly to the use of these derivatives for treatment of human myeloma.
Cancer is a global killer of humans with breast cancer and colon cancer among the leaders with many other types killing modest amounts of humans yearly including human myeloma for which there appears to be no cure.
Myeloma is a cancer of plasma cells. Plasma cells are normally present in the bone marrow and are responsible for antibody production in response to infection and other immune triggering events. In myeloma, a single defective plasma cell (myeloma cell) gives rise to the much larger number of myeloma cells which build up in the bone marrow. This process disrupts the normal immune system as well as displacing the normal bone marrow cells. The myeloma cells divide and grow more frequently than normal plasma cells and develop cancerous properties which enable myeloma cells to invade and damage bone as well as travel through the blood stream to other bone marrow sites. Because there is no known cure, treatments need to be viewed in terms of how long they are able to control the disease or relieve symptoms and how they affect the patient""s quality of life.
There are over 13,500 new cases of myeloma in the U.S. each year representing 20% of blood cancers and 1% of all types of cancer. The incidence varies from country to country from a low 1/100,000 in China to approximately 4/100,000 in most Western industrialized countries.
The U.S. patent literature has many disclosures of oxo-butenoic (crotonic) compounds:
Pamukci (U.S. Pat. No. 6,232,312) describes crotonic acid derivatives (column 22, lines 43-58) for the treatment of colonic polyps;
Jones et al (U.S. Pat. No. 6,121,450) discloses crotonic acid derivatives (column 8, tine 34; column 78, line 24 and at example 34 as steroid modifiers in treating breast cancer (column 1, lines 55-58);
Kalden, et al (U.S. Pat. No. 5,334,612) discloses compounds said to be useful for treating AIDS including derivatives of carboxylic acid (column 9, line 31) and pyrrolidine (column 7, line 24);
Brown (U.S. Pat. No. 6,066,670) describes an anti-viral admixture containing crotonic acid for treating tumors (see Abstract);
Horwell, et al (U.S. Pat. No. 5,580,896) discloses many 4-oxo-2-butenoic acid derivatives (column 13, lines 21-59; also in columns 15+, examples acid derivatives (column 13, lines 21-59; also in columns 15+, examples 25,26,32,34,40,43-46,77-79,97,99,103,106,), which are useful for inhibiting colorectal cancer, i.e., colon cancer (Abstract);
Giordani, et al (U.S. Pat. No. 5,580,890) discloses 4-oxo-2-butenoic acid derivatives said to be useful for treatment of AIDS (column 1, line 8 and column 2, line 61; and,
Yonemeto, et al (U.S. Pat. No. 6,083,985) recites a number of anti-tumor or anti-AIDS agents that include heterocylic butenoic acid derivatives.
The U.S. patent literature has many disclosures of butanoic acid derivatives including:
Nicolai, et al (U.S. Pat. No. 6,180,651) discloses many anti-inflammatory and analgesic compounds, including adenocarcinoma (column 1, line 55), which includes heterocyyclic alcohol-esters (column 11, lines 1-16) and butanoic acid derivatives (many Examples including 47 through 162);
Girard, et al (U.S. Pat. No. 5,308,852) discloses many compounds including butanoic acid derivatives (see Methods B and C of schemes II and III) which compounds which are said to inhibit tumor metastasis (column 7, line 56 and column 8, line 4);
Frechette (U.S. Pat. No. 5,696,117), Frechette(5,854,242) and Frechette (U.S. Pat. No. 5,707,990) describe 148 benzoxazine and pyrido-oxazine heterocyclic as anti-bacterial compounds;
Omedi-Sale (U.S. Pat. No. 3,862,954) shows tri-azole compounds for CNS use;
Hawkins (U.S. Pat. No. 5,274,002) describes many analogs of phenyl ethers of a substituted phenyl of the formula structure at column 1, lines 49-60 with 37 examples of specific compounds which compounds may be useful for tumor inhibition (column 22, line 64); and,
Boyd, et al (U.S. Pat. No. 6,080,790) also describes many tri-substituted phenyl derivatives according to the formula of the Abstract with 15 examples of specific compounds which may be useful for malignant skin diseases (column 5, line 46).
It appears from a review of the foregoing that the oxo-butenoic derivatives of interest are not disclosed and thus there is no report of their activity against human myeloma.
Consequently, there is a need for an anti-cancer drug for humans that mitigates the above mentioned disadvantages of current drug therapy and effectiveness against human myeloma.
The objective of the present invention is to provide a drug effective for treatment of human myeloma.
Preferred embodiments of the invention encompass novel compounds of derivatives of 4-oxo-2-butenoic acid comprising the property of anti-tumor activity against human myeloma and more specifically those novel compounds, alone or in admixture: OF-07; OF-09; OF-10; and OF-20 and the use of the compounds: OF-06, OF-07; OF-09; OF-10; OF-13; OF-20; IF-04; IF-18 and, 3F-19 in humans as therapeutic means for the eradication of the myeloma carcinogens from the human""s body.